Coenzymes Q are essential constituents widely distributed in living bodies, from bacteria to mammals and are known as mitochondrial electron transfer system constituents in cells of living bodies. Through repeated oxidation and reduction in mitochondria, coenzymes Q perform their function as transmitter components in the electron transfer system and, further, reduced coenzymes Q are known to have antioxidant activity. In humans, coenzyme Q10, whose coenzyme Q side chain comprises 10 repeating structures, is the main component and, generally, about 40 to 90% thereof occurs in reduced form in living bodies. The physiological activities of coenzymes Q may be energy production activation through mitochondrial activation, cardiac function activation, cell membrane stabilizing effect, and cell protecting effect through antioxidant activity.
Coenzymes Q are known to be useful in various application fields. For example, oxidized coenzyme Q10 is used as a remedy for congestive heart failure owing to its effects on the heart. Besides such medical uses, they are orally used as nutrients or nutritional supplements, like vitamins. However, coenzymes Q are highly liposoluble and hardly soluble in water and, therefore, only oral preparations and dermal preparations are known as their practical uses.
In recent years, various reports have been published about the aggravation of diseases due to increases in oxidative stress in blood. Typical examples are arteriosclerosis, complications of diabetes and the like diseases. These diseases are caused and/or aggravated by denaturation of lipids and the like due to various oxidative stresses occurring in blood. For counteracting such effects of oxidative stresses, antioxidant activity promotion by administration of an antioxidant is effective. Vitamin E is a compound representative of the liposoluble antioxidant substances considered to be more effective in inhibiting lipid peroxidation and is in wide use in disease prevention and so on.
Recently, it has been reported that the coexistence of reduced coenzyme Q10 is important for vitamin E to properly perform its antioxidant activity (Bowry et al., 1993, J. American Chemical Society, 115, 6029-6044), and the importance of coenzymes Q as liposoluble antioxidant substances is becoming clear.
Coenzymes Q have themselves strong antioxidant activity and, therefore, the antioxidant activity in blood can be effectively enhanced by sending a sufficient amount of reduced coenzymes Q in solubilized form into blood. The enhanced antioxidant activity in blood is considered to be useful widely in preventing vascular lesions during ischemia-reperfusion, preventing restenosis in arteriosclerosis, preventing vascular lesions following cerebral infarction, preventing arteriosclerosis, preventing complications of diabetes, and preventing a number of other diseases from being aggravated supposedly by active oxygen species. Furthermore, by sending it into the living body in a new delivery form, namely by drip, it becomes possible to provide patients with a serious illness or a brain disease, who are incapable of oral intake, with coenzymes Q. It is thus expected that solubilization of coenzymes Q will bring about a number of merits.
As is well known, coenzymes Q can occur in both the oxidized form and reduced form, and a number of investigations have so far been made about the method of solubilizing oxidized coenzyme Q10 (ubidecarenone or ubiquinone).
As for the solubilization of oxidized coenzyme Q10, various methods have been reported, for example coating with liposomes, suspension using a surfactant or an oil/fat, and the like (Japanese Kokai Publication Hei-05-186340, Japanese Kokai Publication Hei-07-69874, Japanese Kohyo Publication 2000-510841). However, few examples have been put to practice use. One of the reasons is that while it is necessary for oxidized coenzyme Q10 to be converted to the reduced form by the action of a reductase or the like in order to perform its antioxidant activity, no reductase is present in blood and, therefore, no antioxidant activity against oxidative stresses in blood can be expected upon administration by injection or the like.
On the other hand, reduced coenzyme Q10 itself has antioxidant activity, hence it is a substance much expected to be of great utility in the prevention/treatment of such diseases as mentioned above. However, it has not been put into practical use because of its drawback that it is susceptible to oxidation and thus unstable. Although a search report describing the preparation of liposome-coated reduced coenzyme Q10 for the purpose of studying oxidoreductases and so forth is available (Kishi et al., 1999, BioFactors, 10, 131-138), the liposomes used were prepared extemporaneously in each experiment. Any method of stably solubilizing reduced coenzymes Q has not been known at all.